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Biomedical subjects

C K Brown

Publications and source records attributed to C K Brown.

At least 73 records · Page 4Linked to original sources

Changes in jejunal myoelectrical activity during exercise in fed untrained dogs.

Seven female dogs (15-20 kg) were instrumented with seven bipolar electrodes sutured at 3-cm intervals to the serosal surface of the proximal jejunum and were exercised at different intensities and durations on a motor-driven treadmill. Slow-wave frequency increased (P less than 0.05) from preexercise control during prolonged (90 min) exercise and during recovery after short-term exercise (30 min) at 70% heart rate reserve (HRR). These changes were associated with an increase in core temperature. Spike-burst frequency (SBF) increased (P less than 0.05) with moderate exercise (50% HRR), but the magnitude was small. When exercise was extended beyond 30 min and during all recovery periods, SBF decreased significantly. Exercise produced migrating myoelectrical complexes in three experiments and less dramatic pattern changes characterized as "clustered contractions" (regular spike bursts preceded and followed by the absence of spike bursts) in at least nine other experiments. We conclude that exercise does alter jejunal myoelectrical activity, but myoelectrical patterns may be more important in explaining exercise-induced gastrointestinal symptoms than changes in spike-burst frequency or duration.

Animals↗

Duodenal resistance to the emptying of various solutions from the isolated cat stomach.

Experiments were conducted to determine to what extent the duodenum resists the emptying of various solutions from the isolated stomach. Cat stomachs were maintained in Krebs solution in vitro, and filled with 100 ml isotonic saline solution, isotonic glucose, hypertonic saline solution, hypertonic glucose, or dilute acid. Gastric pressure was constantly monitored; gastric output was collected constantly by a cannula in the proximal or distal duodenum. For all solutions, cumulative gastric output at all times was considerably less with the distal than the proximal cannula position. This difference was almost entirely caused by a smaller fractional gastric output during the first minute of gastric emptying, and by reduced amplitude of the gastric stroke volume with the distal cannula position. Some differences were observed in the gastric emptying rate for the various solutions; isotonic saline solution emptied particularly slowly and hydrochloric acid emptied particularly fast. In addition, the various solutions produced different gastric pressure patterns, which could not be entirely explained by differences in residual gastric volume. We concluded that the cat duodenum provides a resistance to gastric emptying over and above that generated by the pylorus, and that the duodenal resistance is caused by limitations in duodenal capacity. It is furthermore concluded that the mechanical activity of the isolated stomach and duodenum is affected by the chemical composition of their luminal contents.

Animals↗

Temporal variations of glandular kallikrein, protein and amylase in mixed human saliva.

Variations in the level of glandular kallikrein in human saliva may reflect physiological changes. Diurnal or circadian variations of many salivary components are important in relating changes in such components to oral or systemic conditions especially as most clinical studies are conducted between 0800 and 1700 h. Whole saliva was collected from 14 healthy young subjects at 0800, 1100, 1400 and 1700 h on two Fridays. Samples were centrifuged at 10,000 g for 10 min at 4 degrees C and the supernatant fractions stored at -20 degrees C. The enzymic activity of kallikrein was measured with D-valylleucylarginine-p-nitro-anilide as substrate. The activity of alpha-amylase and the total protein concentration (biuret) were also determined. Results were analysed in a repeated-measures design: there were no significant differences in kallikrein levels either within days or across days. There were significant differences for total protein and alpha-amylase levels within days but, in general, not across days. Minimal individual levels for protein and alpha-amylase were mostly at 0800 h; maxima were generally at 1400 or 1700 h. Kallikrein levels had no marked pattern of maximal or minimal distribution.

Amylases↗

Upper lip, lower lip, and jaw interactions during speech: comments on evidence from repetition-to-repetition variability.

Six studies purporting to demonstrate complementary covariation in lip and jaw activity during speech are reviewed. The statistical procedures used to assess interactions among the upper lip, lower lip, and jaw movements are discussed for four different experiments analyzing repetition-to-repetition movement variation. The findings from two studies analyzing repetition-to-repetition variation for interactions in electromyographic activity recorded from either the jaw musculature or the labial musculature also are evaluated. It is concluded that these studies do not provide convincing evidence of complementary covariation among the articulators or the muscles.

Jaw↗

The creation and repair of diaphragmatic hernia in fetal lambs: morphology of the type II alveolar cell.

A model for creating and repairing diaphragmatic hernia in fetal lambs has been developed. Morphometric studies of the type II alveolar cells were carried out in three groups of term lambs. The upper lobes only were sampled. Morphometric analysis of the 30 type II cells from each lobe showed that while there were no differences between the left upper lobe (LUL) and right upper lobe (RUL) cells in normal lambs, there were significant differences between sides in the experimental groups. In lambs with a nonrepaired diaphragmatic hernia (DH) the type II cells were significantly smaller in the LUL compared with the RUL. In lambs with a repaired DH, the LUL type II cells were significantly larger than those in the RUL. There were some trends when the groups were compared, but in general they did not reach statistical significance. These findings suggest that local factors profoundly influence the development of these cells.

Animals↗

Emptying of saline meals by the cat stomach as a function of pyloric resistance.

The effect of the pylorus on the rate of gastric emptying and on the pattern of flow from the stomach to the duodenum was studied. Cat stomachs were filled with 50, 100, or 150 ml of 0.9 N saline, and intragastric pressure and gastric fluid output were monitored continuously. The tip of the collecting cannula was positioned either in the duodenum thus allowing the pylorus to close) or in the pyloric segment thus preventing the pylorus from interfering with gastric outflow). Initial experiments demonstrated that fluid output was similar for the cat stomach in situ and in vitro. Incremental output (i.e., the absolute volume emptied per collection period) increased with the meal size and was proportional to the fluid volume actually remaining in the stomach; fractional gastric output (i.e., the volume emptied as a percentage of the actual gastric volume) did not change with meal size. The half time for gastric emptying was greater with the collecting cannula positioned in the duodenum than in the pylorus (e.g., with the 100-ml meal, 154 vs. 46 s). With the cannula in the pylorus, gastric outflow was constant and ceased only when gastric emptying had terminated. With the cannula in the duodenum, outflow was pulsatile and ceased intermittently at gastric volumes that were subsequently emptied. We conclude that the cat pylorus renders the outlet of the stomach continent even to liquids; furthermore, the pylorus imparts a pulsatile pattern to flow of liquids from the stomach to the duodenum.

Animals↗

Bladder cancer risk among auto and truck mechanics and chemically related occupations.

Male participants in the NCI National Bladder Cancer study were evaluated for risks in auto and truck mechanic and in chemically related exposure occupations compared with those who had never worked in these areas. In nonsmokers the adjusted rate ratios (RR) for mechanics equalled 1.33, (95% CI 0.77, 2.31). The adjusted RR in the nonsmoker chemically related group was 1.53 (95% CI 1.13, 2.07). Duration of exposure as a mechanic was not clearly associated with bladder cancer risk regardless of smoking status.

Adult↗

Visual function abnormalities in central serous retinopathy.

Eighteen patients with central serous retinopathy (CSR) underwent a battery of visual function tests when first seen and after resolution of the subretinal fluid. Eyes with CSR had minimal relative afferent pupillary defects, reduced critical flicker-fusion thresholds, prolonged visual evoked potential (VEP) latencies, increased errors on the Farnsworth-Munsell 100-hue (FM 100) test, and depressed central visual fields (Octopus). The afferent pupillary defect and critical flicker-fusion thresholds were the first to improve after resolution of the subretinal fluid. Next in rate of improvement were the visual acuity, the VEP latency, and the FM 100 test results. The threshold of the central Octopus at fixation improved the slowest and was still abnormal during long-term follow-up, indicating a prolonged depression in the threshold of central field sensitivity after resolution of the CSR. Many of these abnormalities are also seen in patients with optic nerve disease.

Adult↗

Predicting age of onset for individuals at risk for phakic retinal detachment.

Three hundred sixty-five cases of nontraumatic phakic retinal detachment were examined by analysis of covariance to determine the degree of association among type of detachment, refractive error, and age of onset. The combination of type of detachment and refractive error explained 57% of the variation in age of onset. Discrimination among types of detachment by variation in mean age was limited. Discrimination among types of detachment by variation in mean refractive error could not be established. Detachments due to vitreoretinal adhesion, lattice degeneration, and retinal dialysis differed significantly in mean age of onset and regression of age on refractive error. A regression model was created to predict from refractive error the age of onset with 95% confidence limits for individuals who appear to be at risk for these types of detachment.

Adolescent↗

Epidemiology of retinal detachment.

A survey of rhegmatogenous retinal detachment during 1976 was conducted on the population of Iowa. The annual incidences (per 100,000 populations) of four types of detachment were determined: nontraumatic phakic (6.1), traumatic phakic (1.0), nontraumatic aphakic (4.9), and traumatic aphakic (0.4). The incidences of nontraumatic phakic detachment for men and women were similar, although there was a preponderance of women that reflected their greater representation in the general population. The proportions of men were significantly higher in traumatic detachments compared with nontraumatic detachments. Men tended to be younger than women for all types of detachment; however, only in nontraumatic aphakic detachment was there a significant difference between mean ages. There was an insignificant preponderance of right eye involvement in all four detachment groups.

Adolescent↗

2-bromo-alpha-ergocryptine (CB-154) and tamoxifen (ICI 46,474) induced suppression of the genesis of mammary carcinomas in female rats treated with 7,12-dimethylbenzanthracene (DMBA): a comparison.

Daily treatment of female Sprague-Dawley rats with CB-154 (prolactin suppressor) or Tamoxifen (estrogen antagonist) for 33 days before and after 7,12-dimethylbenzanthracene (DMBA) administration reduced (p less than 0.005) the incidence of mammary carcinomas by 58 and 49%, respectively. A combination of CB-154 and Tamoxifen further reduced (p less than 0.005) mammary carcinoma incidence by an additional 50-59%. Treatment with Tamoxifen for 66 days beginning 33 days after carcinogen treatment reduced (p less than 0.05) the incidence of mammary carcinomas by 65%; CB-154 treatment, during the same time period, did not significantly effect the final yield of mammary carcinomas. The combination of Tamoxifen and CB-154 was comparable to Tamoxifen alone in suppressing the incidence of mammary carcinomas in the latter study. These results demonstrate a substantial suppressive and synergistic effect of Tamoxifen and CB-154 in the initiating phases of mammary carcinogenesis while in the early promoting phases of this oncogenic process, short-term treatment with Tamoxifen was superior to CB-154 treatment; no synergism between these clinically important compounds was observed.

9,10-Dimethyl-1,2-benzanthracene↗

The prophylaxis of rat and mouse mammary gland tumorigenesis by suppression of prolactin secretion: a reappraisal.

The purpose of this study was to evaluate the effect of early and temporal CB-154 induced suppression of prolactin secretion on the genesis of mammary tumors in female Sprague-Dawley rats treated i.g. with 3 doses of 7,12-dimethylbenzanthracene (DMBA); doses which yield a high (20 mg), moderate (5 mg) and low (1.25 mg) mammary carcinoma incidence. In addition, the effect of prolactin suppression on the genesis of mammary tumors in strains of rodents which, when treated with maximally tolerated doses of DMBA, develop a moderate (female Lewis rats) and a low (female Long-Evans rats and female Balb/c mice) mammary carcinoma incidence was also evaluated. Daily suppression of prolactin secretion during DMBA treatment (30 days before, during and 30 days after) (series 1) or commencing 30 days after DMBA treatment (for 60-81 days) (series 2) significantly (P less than 0.05) reduced the number of mammary carcinomas in Sprague-Dawley rats treated with 20 and 5 mg DMBA and in Lewis rats (series 2); treatment with CB-154 did not significantly lower mammary carcinoma incidence in Sprague-Dawley rats treated with 1.25 mg DMBA, nor in Lewis rats (series 1), Long-Evans rats and Balb/c mice. These results provide evidence that the effectiveness of prolactin suppression in the prophylaxis of chemical carcinogenesis of the rodent mammary gland is enhanced when a moderate or large dose of the carcinogen is used, or a strain of rodent is used which is moderately or highly susceptible to the mammary oncogenic effects of the carcinogen. Low doses of the carcinogen or use of a rodent strain relatively resistant to the carcinogen nullifies the chemopreventive activities of early prolactin suppression.

9,10-Dimethyl-1,2-benzanthracene↗

Selenium and the genesis of murine mammary tumors.

One hundred forty-seven female Sprague-Dawley rats were divided into 5 groups and at 60 days of age were treated i.g. with 5 mg of 7,12-dimethylbenzanthracene (DMBA) suspended in 1.0 ml of sesame oil. Selenium (Se), as selenium dioxide (SeO2), was administered in the drinking water to 4 of the 5 groups (30 rats/group) at 2 doses (2 and 4 mg/l) from 30-90 days of age (series 1) and from 90-150 days of age (series 2) prior to the onset of palpable mammary tumors. One group of rats (27 rats) served as controls. All rats were palpated weekly for mammary tumors and sacrificed 28 weeks after DMBA treatment. Total number of palpable mammary carcinomas which developed in each group were: controls, 60; series 1, 2 mg Se dose, 27, 4 mg Se dose, 29; series 2, 2 mg Se dose, 24, 4 mg Se dose, 32. Each dose level of Se in each series significantly (P less than 0.05) reduced the incidence of mammary carcinomas. These results provided evidence that Se can inhibit the early promoting phases of polycyclic hydrocarbon induced mammary carcinogenesis in female rats. Two hundred twenty-six nulliparous and 99 multiparous GR mice were treated daily with estrogen and progesterone for 13-16 weeks. Se (SeO2) was administered in the drinking water (2 mg/l) to one-half of these mice. Total number of mammary carcinomas in control nulliparous and multiparous mice were 119 and 90, respectively; in Se treated nulliparous and multiparous mice, 113 and 81, respectively. Se did not significantly effect mammary carcinoma incidence in hormone treated nulliparous and multiparous GR mice.

9,10-Dimethyl-1,2-benzanthracene↗

Enhancement by retinyl acetate of hormone-induced mammary tumorigenesis in female GR/A mice.

Feeding of retinyl acetate (82 mg/kg ration) for 13-16 weeks to estrone- and progesterone-treated nulliparous and multiparous inbred GR/A mice resulted in a substantial increase in the incidence of mammary carcinomas. Mammary carcinoma incidence in nulliparous control and retinoid-fed mice in experiment #1 was 22/65 (34%) and 37/65 (57%) (P less than 0.05), respectively; in experiment #2, 27/48 (56%) and 37/48 (77%) (P less than 0.05), respectively. Mammary carcinoma incidence in multiparous control and retinoid-fed mice in experiment #1 was 13/30 (43%) and 23/30 (77%) (P less than 0.05), respectively; in experiment #2, 19/19 (100%) and 19/19 (100%), respectively. The purported chemopreventive activities of retinyl acetate in murine mammary tumorigenesis were not demonstrated in this study; indeed, the vitamin A analog appeared to enhance this oncogenic process in the steroid hormone-treated GR mouse mammary cancer model.

Animals↗

Synergistic effect of chronic prolactin suppression and retinoid treatment in the prophylaxis of N-methyl-N-nitrosourea-induced mammary tumorigenesis in female Sprague-Dawley rats.

Two hundred forty Sprague-Dawley rats were treated i.v. with 2.5 or 1.25 mg of N-methyl-N-nitrosourea (MNU) per 100 g body weight at 50 and 57 days of age. At 60 days of age, rats given either dose were divided into 4 groups (30 rats/group) and treated as follows: Group 1, controls; Group 2, 0.4 mg 2-bromo-alpha-ergocryptine (CB-154) per 100 g body weight injected s.c. once daily; Group 3, retinyl acetate (328 mg/kg diet) fed daily; and Group 4, CB-154 and retinyl acetate treatments combined. Rats that received the 2.5-mg dose of MNU were treated for 129 days; those that received the 1.25-mg dose of MNU were treated for 175 days. The rats that were treated with the high dose of MNU were maintained without any treatment for an additional 13 weeks, after which they were sacrificed. The rats that were treated with the low dose of the carcinogen were sacrificed immediately after treatment. All rats were palpated once weekly for palpable mammary tumors. The number of rats with mammary tumors and the total number of mammary tumors at cessation of treatments were, respectively, as follows. MNU (2.5 mg): Group 1, 22 of 30 (73%), 82: Group 2, 11 of 30 (37%), 17; Group 3, 11 of 30 (37%), 19: Group 4, 2 of 30 (7%), 2. MNU (1.25 mg): Group 1, 8 of 30 (27%), 14; Group 2, 4 of 30 (13%), 5; Group 3, 3 of 30 (10%), 4; Group 4, 0 of 30, (0%), 0. Thus, chronic CB-154 treatment or retinyl acetate feeding markedly reduced the percentage of rates bearing mammary tumors and the total number of mammary tumors. The combined treatments were superior to either treatment alone, inasmuch as mammary tumorigenesis was nearly completely blocked in the rats of Group 4 that received the 2.5-mg dose of MNU and was totally blocked in the rats of Group 4 that received the 1.25-mg dose of MNU. Retinyl acetate feeding or CB-154-induced prolactin suppression appear to be equally effective treatments in the prophylaxis of MNU-induced mammary tumorigenesis in rats; the combined modality, however, appears to be far superior than either treatment alone.

Adrenal Glands↗

Inhibition of mammary tumorigenesis in GR mice with 2-bromo-alpha-ergocryptine.

A high incidence of mammary tumors is found in multiparous GR mice during the 2nd and 3rd pregnancies and in nulliparous GR mice treated with estrone/progesterone. The purpose of this study was to determine if prolactin is a contributing hormone in the genesis of these neoplasms. In one series of experiments, 238 15-week-old nulliparous GR mice were treated with estrone (drinking water, 0.5 mg/liter) plus progesterone (30 mg progesterone pellet with cholesterol, implanted SC once monthly) for a period of 13 weeks. Half of these mice were injected SC once daily with 100 micrograms of the prolactin-suppressing drug 2-bromo-alpha-ergocryptine (CB-154) for the duration of hormone treatment, and the other half were injected SC once daily with 0.9% NaCl solution (controls). In another series of experiments, 87 pregnant GR mice were divided into two groups and injected SC once daily from day 7 to 21 of pregnancy with 0.9% NaCl solution (controls) or CB-154 (100 micrograms/mouse). In the first series, the numbers of mice with mammary tumors and total number of mammary tumors were: controls, 58/119 (49%) and 73; CB-154 treatment, 34/119 (29%) and 37, respectively. In the second series, the numbers were: controls, 39/44 (89%) and 73; CB-154 treatment, 24/43 (56%) and 43, respectively. In both studies, CB-154 treatment significantly (p less than 0.05-0.005) reduced the percentage of mice with mammary tumors and total number of mammary tumors. These results provide evidence that prolactin is a contributing hormone in the genesis of estrone/progesterone and pregnancy-induced mammary tumors in female GR mice.

Animals↗